A vessel for storing a medicament has been made of glass and is recently made of plastics. An opening of the vessel is sealed with a stopper made of a material which has good resistance against heat and compressive strain, flexibility and is chemically inactive and non-permeable to gasses such as oxygen, nitrogen, carbon dioxide and water vapor.
As the stopper material, G. K. Merinikowa proposed an elastic copolymer of isoprene and isobutylene (hereinafter referred to as "IIR"). Further, to improve the properties of the stopper, there are proposed several manners such as compounding of polyethylene fine powder in a rubber, co-crosslinking of chlorinated butyl rubber and nitrile rubber, use of a styrene-butadiene-styrene block copolymer, a coating of a silicone type compound or a fluorine-containing compound on the molded rubber stopper and laminating of the stopper with a film of polypropylene, polyethylene, polyamide and fluororesin (cf. Japanese Utility Model Publication Nos. 27753/1969, 17831/1970, 21346/1974 and 28207/1979 and Japanese Patent Publication Nos. 1355/1977, 9119/1979 and 53184/1982).
Although the silicone type compound and the fluorine-containing compound reduce the adhesivity of the surface of the stopper, they cannot completely be coated on the surface of the stopper so that the coated stopper has, as the stopper of the vessel for the medicaments, poor chemical and physical properties, particularly, the number of fine particles.
On the contrary, the laminated rubber stopper has better chemical and physical properties. However, precise investigation of the laminated stopper revealed that the fluororesins such as polytetrafluoroethylene have unsatisfactory moldability and/or mechanical strength, require many steps to laminate it on the stopper and have poor adhesivity on the rubber surface.
To overcome such drawbacks of the laminated stopper, it is proposed to use a fluorine-containing copolymer as a laminating material and to laminate it simultaneously with vulcanization of the stopper rubber (cf. Japanese Patent Kokai Publication (unexamined) No. 5046/1984). This method is superior as a method for producing a rubber stopper. As the preferred fluorine-containing copolymer, exemplified are tetrafluoroethylene/ethylene alternating copolymers and tetrafluoroethyolene/hexafluoropropylene copolymers. Although the conventional tetrafluoroethylene/ethylene alternating copolymer has comparatively large tensile strength and elongation at a vulcanizing temperature and satisfactory processability during laminating the stopper, failure rate of the resin film in the production of the laminated rubber stopper is still unsatisfactory. In addition, since elasticity and compressive strain resistance of the rubber are deteriorated due to hardness of the resin film, the produced laminated stopper has poor fitting with the opening of the vessel, which may result in some troubles such as air leak in formulation of a medical preparation under reduced pressure. Further, the fluororesin film has unsatisfactory sealing property. The tetrafluoroethylene/hexafluoropropylene copolymer has poorer laminating moldability and adhesivity with the rubber since it has worse mechanical properties at or about a molding temperature than the tetrafluoroethylene/ethylene copolymer.
Standards to be satisfied by a stopper of a vessel for medicaments are defined by, for example, Japanese Pharmacopoeia, 10th Edit., British Standards 3263 (1960) and DIN. However, these standards are not suitable for prolonged storage of medicaments having high quality. Further, since methods for formulating medicaments are greatly improved, the stopper plays a more important role in the pharmaceutical field.
The properties to be satisfied by the stopper are roughly classified into chemical ones and physical ones. An example of the material having excellent chemical properties is a fluororesin. However, as described above, it does not necessarily satisfy all the physical properties such as flexibility, moldability and adhesivity.